Flashcards in Module 5: Endocrine: Adrenal Cortical Adenoma, Pheocyto Deck (39):
First starting off, what is an adrenal cortical adenoma?
--Non-functional (asymptomatic) called an incidentaloma
--Benign neoplasm of the adrenal glands -- is usually non functional but can be functional
Describe the functional aspect of adrenal cortical adenoma
Zona Fasciculata --- cortisol production ----Cushings (ACTH low due to negative feedback so contralateral adrenal atrophy)
Zona Glomerulosa -- aldosterone (Conn's syndrome) --primary hyperaldosteronism
Zona Reticularis-- androgens
women: virilization and hirsutism and FCC and endometrial cancer due to the excess estrogen made by the androgens
What is the triad of symptoms if a patient develops Conn's Syndrome in the Zona Glomerulosa?
1. Malignant Hypertension: resorption of sodium and water in the distal tubule; normal sodium levels and low renin levels (neg feedback)
2. Hypokalemia (muscle cramps and weakness)
3. Metabolic Alkalosis
What is secondary aldosteronism?
From outside the adrenal gland
--renin and aldosterone are both elevated
What are causes of secondary aldosteronism?
2.Renal Artery Stenosis
3.Liver Cirrhosis (no albumin production-- fluid trapped in tissues --- hypoperfusion to kidneys --renin secretion)
4.Nephrotic Syndrome: albumin is lost in the urine (fluid trapped in tissues -- hypoperfusion to kidneys--renin secretion)
5.Congestive Heart Failure
Moving on to pheochromacytoma, what is the etiology?
Etiology: Tumor of adrenal medulla (chromaffin cells)
cell of origin: chromaffin neural crest cells (benign or malignant) (NOT ENTEROCHROMAFFIN thats GI)
What is the rule of 10 in pheochromacytoma?
10% in children
20-25% familial (MEN 2A, MEN 2B, VHL, Neurofibromatosis)
--what else do VHL? Retinal and Cerebellar Hemangioblastomas and Clear Cell Renal Carcinoma
What is the presentation for a patient with pheochromocytoma?
Mimics hyperthyroidism and Graves
--episodic malignant hypertension
--palpitations (most common cause of death)
What makes the symptoms worsen in pheochromocytoma?
Pressure on abdomen
--all due to the release of catecholamines
What investigations are done for pheochromocytoma?
Never do a CT first
Elevated catecholamines in the blood and urine
BMA and metanephrines in the urine are catecholamine metabolites
--VMA is catecholamine metabolite for neuroblastoma
--Metanephrine is catacholamine metabolite for pheochromocytoma
CT is next of adrenal to locate: 10% is extra adrenal and 90% is adrenal medulla.. what if you see nothing??
not found there----MIBG (radioisotope scan) ---Carotid Bodies typically (this is the most likely location of extra adrenal sites)
What is seen on gross and histology for pheochromocytoma?
Gross: Brown is taking over the medulla (takes over the entire adrenal gland)
Histology: Nests of spindle shaped chromaffin cells separated by scanty vascularized stroma (Zellballen)
What are the complications in pheochromocytoma?
HTN -- atherosclerosis --- hypertrophy of LV--- LV failure --- RV failure -- mural thrombosis--- atrial fibrilation -- emboli stroke
Arrhythmias is the most common cause of death
What should happen in surgery patients with pheochromocytoma?
Should be alpha blocked then beta blocked
--alpha receptors on blood vessels --- vasoconstriction -- stroke MI
alpha blocks allow vasodilation
beta receptors are located on the heart (if blocked first, all catecholamines would go to alpha receptors and cause massive vasoconstriction)
The primary etiology of HTN in endocrine disorders is idiopathic. However, what are some secondary causes?
Acromegaly: GH upregulates alpha 1 receptors
Cushing's Disease: cortisol is weak mineralcorticoid and upregulation of alpha 1 receptors
Pheochromocytoma: production of epinephrine and norepinephrine
Conn's Syndrome: due to adrenal cortical adenoma affecting ZG
Next we will briefly discuss neuroblastoma in kids. What is a neuroblastoma?
Poorly differentiated tumor of NCCs that normally give rise to the adrenal medulla and sympathetic ganglia due to germline mutation in ALK gene.
--second most common solid malignant tumor in children
What is the presentation of a patient with Neuroblastoma?
less than 2 years old: mass in abdomen or mediastinum, fever, weight loss, and constipation
Older kids: signs of metastatic disease (bone pain, resp, GI symptoms)
What investigations are done for neuroblastoma?
Gross calcification in 40-50%
Microscopy: neuropil (eosinophilic fibrillary material) and Homer-Wright Pseudorosettes (tumor cells arranged around neurophil with no lumen)
EM: neurosecretory granules
IHC: neuron-specific enolase and synaptophysin
What are clues for diagnosis of a neuroblastoma?
Increased blood catecholamines
Increased urine levels of catecholamine metabolites (VMA and HVA)
MIBG scintigraphy: concentrates in over 90% of tumors -- used for assessment of spread and response to therapy
What are the good prognostic factors for a neuroblastoma?
Stage 45 and increased expression of Tyrosine kinase receptor A
What are the bad prognostic factors for a neuroblastoma?
Deletion distal 1p and gain of distal 17q; n-myc amplification and telomerase overexpression
One of the etiologies for hypercalcemia is hyperparathyroidism, explain this
Primary: solitary adenoma
Secondary: reaction of parathyroid glands to a hypocalcemia
Tertiary: increased PTH to maintain normocalcemia in the setting of vit D deficiency --- parathyroid hyperplasia occurs and PTH secretion becomes independent of calcium level
--part of MEN1 and MEN2 syndromes
What are the other etiologies of hypercalcemia?
Excessive Vitamin D
Granulomas (TB, lymphoma, sarcoidosis): b/c they activated vit D
High Bone turn over: thyrotoxicosis and Pagets disease
In about 50% of ppl become asymptomatic in hypercalcemia, explain the symptoms in each organ system
Renal: polyuria and thirst, stones, nephrocalcinosis and renal failure
Musculoskeletal: muscle weakness, osteitis fibrosa cystica
Neurological: psychiatric/neurological symptoms
GI: anorexia, constipation and ulcers
What is treatment for hypercalcemia?
Correct dehydration, frusemide, biphosphonates and calcitonin
Moving onto hypocalcemia, explain PTH related etiology
PTH-related: hypoparathyroidism, pseudo-hypoparathyroidism and hypomagnesemia
--pseudo-hypoparathyroidism/Albright's Hereditary Osteodystrophy: decreased responsiveness of kidney due to defective PTH receptors --- decreased calcium and increased phosphate
What are other etiologies for hypocalcemia?
Hypoalbuminemia: decreased total plasma calcium but ionized calcium is normal
Chelation by EDTA
Defect in Vit D metabolism: rickets, osteomalacia, chronic renal failure and liver disease
What is the presentation for hypocalcemia?
Increased neuromuscular excitability: tetany, paresthesia, and cramps
Prolonged hypocalcemia: cataracts, mental retardation, psychosis, increased ICP and seizures
What are some etiologies for hypophosphatemia?
Increased cellular uptake: DKA, hyperalimentation, alkalosis
Increased excretion: hyperparathyroidism, hypomagnesemia, renal tubular defect and dialysis
Dilution: volume expansion
Chronic alcohol abuse
What is the presentation for hypophosphatemia?
Hemolysis: depletion of 2,3 diphosphoglycerate
What are etiologies for hyperphosphatemia?
Artifact: hemolysis or delay in separation of blood samples
Chronic renal failure
What is the presentation for hyperphosphatemia?
High plasma calcium and phosphate -- metastatic calcification (Deposition of calcium in previously normal tissues)
What is the etiology for hypomagnesemia?
Etiology: malabsorption, malnutrition and alcoholism
What is the presentation for hypomagnesemia?
What is the etiology for hypermagnesemia?
What is the presentation for hypermagnesemia?
greater than 6mg/L -- respiratory paralysis and cardiac arrest
How do you tell the difference between benign and malignant pheochromocytoma?
They both invade
Congenital adrenal hyperplasia (CAM) is caused by three enzyme deficiencies, each card will go through one. First is 21 alpha hydroxylase deficiency, what are some features
Most common form of CAM
--partial and virtually complete deficiencies are known
--mineralocorticoids and glucocorticoids are virtually absent (salt wasting or deficient)
--overproduction of androgens leads to masculinization of external genitalia in females and early virilization in males
The second cause of CAM is 11 Beta hydroxylase deficiency, what are some features?
Decrease in serum cortisol, aldosterone and corticosterone
--increased production of deoxy-corticosterone causes fluid retention. because this hormone suppresses the renin/angiotensin system, it causes low renin HTN
--overproduction of androgens causes masculinization and virilization as with 21 alpha hydroxylase deficiency